Sensorineural hearing loss is directly related with quality of life, and thus, become a health-related issue which is rapidly emerging in worldwide. Approximately 5% of the world population is troubled with hearing loss caused by noise exposure with high intensity, and as lifespan is increased, occurrence of the sensorineural hearing loss depending on aging has been on the rise every year. Noise-induced hearing loss (NIHL) is one of the most common occupational diseases in advanced countries and developing countries. A lot of researches for preventing and treating the NIHL have been conducted by understanding pathophysiological mechanisms of apoptosis in the cochlea due to noise.
According to those proposed in many of accumulated researches, a representative cause of main causes in the occurrence of the sensorineural hearing loss is apoptosis of hair cells caused by an inflammatory response generated in the cochlea as a hearing organ. The inflammatory response in the cochlea is a response in which fiber cells present in the spiral ligament of the cochlea, support cells of Corti's organ, or immune cells such as macrophages and leukocytes in the blood act to the damaged sites to remove antigens or remove damaged tissues, thereby helping recovery of a normal state, when the damage to constituted tissues is generated by penetration of external substances such as virus or bacteria or strong pressure such as noise. Acute inflammation may be cured in a short period, but in any case, when infection or damage is continuously maintained, the immune cells are continuously left. Accordingly, mediators such as chemokines and cytokines are secreted to damage the surrounding tissues and cause chronic inflammatory diseases such as Allergy, autoimmune, and pancreatitis. The inflammatory response mediators are substances that promote the inflammatory response while the inflammatory response starts and proceeds. The inflammatory response mediators are generated in neutrophils, immune cells such as macrophages, and platelets and include chemokines, cytokines, fat-soluble mediators, and the like. Eicosanoid is a fat-soluble mediator originated from the cell membrane to promote the inflammatory response. The eicosanoid is synthesized from arachidonic acid, a cyclooxygenase (COX) pathway generates many prostaglandins (PGs) and thromboxanes (TXs), and a lipoxygenase (LOX) pathway generates leukotrienes (LTs) and lipoxins (LXs). The LTs are divided into cysteinyl leukotrienes (CysLTs; LTC4, LTD4, and LTE4) and LTB4, CysLTs are known as a representative cause of allergic rhinitis and asthma, and found to be involved to the occurrence of neurodegenerative disorders and cardiovascular diseases according to a recent report. However, all the eicosanoid do not cause or continue the inflammatory diseases, and in the case of PGD2 or 15d-PGJ2, anti-inflammatory effects are reported a lot. Thus, possibility that blocking of a lower pathway based on characteristics for each disease or for each tissue is successful as an effective treatment method is higher than broad inhibition of generation of the eicosanoid.
In the case of existing noise exposure, wearing of hearing protection devices (HPD) is a unique prevention method, but the wearing in the actual industrial sites is limited due to the disadvantages that communication between operators is blocked under a noisy environment. Accordingly, many researchers conduct continuous researches for the discovery of orally administrated drugs for treating and preventing hearing loss in order to overcome these limitations, but orally administrated drugs having clear effects on noise-induced hearing loss or presbycusis are not developed.